GBD study finds reduced heart disease risk with moderate drinking and confirms J-curve

A new study re-evaluated the association between the consumption of alcoholic beverages and ischemic heart disease (Nature Communications on 14 May 2024).

This is the first study were the new Burden of Proof  meta-analytical framework was applied to the consumption of alcoholic beverages as a risk factor. The authors conducted an updated systematic review and re-evaluated existing observational, case-control and Mendelian RandomizationThe basic idea of the Mendelian randomization is to use genetic variables as instrumental variables ... study data with alcohol as a risk factor. This method systematically tests and adjusts for common sources of bias defined according to specific criteria. To date, the approach has been applied to 21 other risk factors, including smoking, second hand smoke, and 14 dietary patterns.

When all 122 observational studies – published between 1970 and January 2021, were pooled in the analysis, the authors found a J-shaped relationship where a consumption of up to about 50g/day was associated with lower risk of ischemic heart disease (IHD) morbidity and mortality and myocardial infarction (MI) morbidity.

Depending on the study design, the decreased risk was different:

• The risk in observational (cohort) studies decreased by 5%
• Among case-control studies the risk was decreased by 13%
• Among the 4 Mendelian randomization (MR) studies that were included in the analysis, no relationship with IHD risk was observed. MR uses genetic proxies (*) instead of measuring alcohol consumption.

The authors evaluated their assessment of the strength of the evidence for these relationships with a star rating from one (weak) to five (strong). Their ratings, along with their conservative relative risk estimates, are summarised in the table below:

Authors’ conservative interpretation of the average risk decrease over the most prevalent average consumption amounts (between 0 and 50g/day).

Conclusions

• This Burden of Proof study used a more advanced meta-analytical technique involving modelling, showing that a J-shaped association exists between the consumption of alcoholic beverages and IHD with a nadir of approx. 23 alcohol/d.
• This robust approach to examine the evidence and address several important potential biases confirmed the results of previous research findings: a J-shaped relationship between alcoholic beverages and IHD in studies using traditional observational methods but not in newer methods, such as Mendelian randomization.
• Various criteria were used to adjust for common sources of bias, such as exposure assessment, which was quantified by whether alcohol consumption was recorded once or more than once in observational studies. Even though this improved meta-analytical methodology considers alcohol assessment, it still does not adjust for factors like drinking frequency/drinking pattern, type of alcoholic beverage and underreporting.
• The study also shows that MR studies are not able to correctly describe a complex association as the one between alcohol consumption and IHD. The authors indicate that MR studies are not fit to study the alcohol-IHD association nor the association between any other disease or total mortality with alcohol consumption.
• To enhance the strength of this evidence, the authors recommend that existing data from cohort studies be used to mimic controlled trial study designs, and that MR studies apply existing guidelines and tests to ensure they meet the necessary assumptions for the method.

The authors note a few limitations in their study, including that there is potential for bias in all three study designs and that they could not investigate the effects of heavy episodic drinking on IHD.

In addition, most of the underlying studies were conducted in Europe (60) and North America (39) with a smaller number conducted in Asia (20), Oceania (5), and South America (2), and the generalizability of their results to countries and regions with limited representation in research is unknown.

(*) Genes vary across a population and these variations can influence behavior (known as a ‘genetic proxy’ for the behavior). In MR, researchers use these genetic proxies to see if certain behaviors are linked to health outcomes, such as specific diseases. Scientists have identified several gene variants that affect the way people process alcohol leading to unpleasant symptoms (e.g. facial flushing) and which are generally associated with reduced alcohol consumption. Researchers have exploited this effect as a ‘genetic proxy’ for alcohol consumption and compare health outcomes between people with and without these genes.